Reactions of Radical Anion and Cations: an Overview

International Journal of Advanced Scientific Research and Management, Volume 4 Issue 1, Jan 2019 www.ijasrm.com

ISSN 2455-6378

Reactions of Radical Anion and Cations: An Overview

Dr. Sayantan Mondal Assistant Professor Department of Chemistry, Bankura Zilla Saradamani Mahila Mahavidyapith, Bankura, West Bengal-722101, India

Abstract substituted phenyl cyclopropyl ketones was first Radical reactions occur through the intermediacy of reported by Tanko and co-workers (Scheme 1) [1]. odd electron species, and are among the key For R = alkyl or hydrogen, ring opening of 1˙ˉ is fundamental classes of organic transformations. Such very slow and reversible with an equilibrium processes play important roles in mechanistic and constant favoring the ring-closed radical anion (ko < synthetic organic chemistry and are essential for 10s-1 and Keq = ko/k-o = 10-8 for R =H). many biological and materials applications. In this Placement of radical-stabilizing substituents (R = review the cationic and anionic mode of reactions of phenyl or vinyl) on the cyclopropyl group partially radicals in organic molecules have been discussed in compensates for this loss of resonance energy, and details with their mechanistic development. ring opening becomes more favorable (ko ~ 106-107 Keywords: Radical-cations, radical-anions, intermediate, s-1 for R = CH=CH2 or Ph). ring closure, electron transfer processes

1. Introduction

The use of small organic molecules to catalyze asymmetric transformations has been known since the early 1970’s (e.g. the Hajos-Parrish-Eder-Sauer- Wiechert Reaction). However, the recognition of this reaction’s mechanism as a general mode of carbonyl Scheme 1. Phenyl cyclopropyl ketones radical anion activation was overlooked. In 2000, general modes ring opening. of activation using small organic molecules (secondary amines) were introduced, namely Radical anions can also be generated from aliphatic enamine and iminium ion catalysis. Recently, ketones. Radical anions derived from 2a and 2b catalysis based on single-electron oxidation of undergo cyclopropane ring opening, slightly favoring transiently produced, electron rich enamines has the 3° distonic radical anion (Scheme 2). Electron introduced a new mode of activation termed SOMO transfer was found to be the rate limiting step organocatalysis. Activation by this method allows for regardless of whether the reduction was carried out reaction with a variety of weakly nucleophilic directly (CV) or indirectly (homogeneous redox substrates incompatible with previous methods. For catalysis) suggesting a rate constant for ring opening > successful SOMO organocatalysis, an equilibrium 107 s-1. Because the kinetics of reduction of 2a and population 2b involve rate limiting electron transfer, the rate constant for ring opening could not be determined.

2. Recent Developments and reactions of Radical ions

Over the past several decades, radical ions have emerged as an important class of reactive species. Scheme 2. Ketyl radical anions ring opening Their role as potential intermediates in numerous organic and bio-organic reactions and development An important reaction involving radical anion of new synthetic methods based on their chemistry intermediates of is the unimolecular radical has attracted significant attention. In 1990, the nucleophilic substitution (SRN1) reaction. The SRN1 chemistry of radical anions generated from mechanism was first proposed for the substitution of 59

International Journal of Advanced Scientific Research and Management, Volume 4 Issue 1, Jan 2019 www.ijasrm.com

ISSN 2455-6378

alkyl halides bearing electron-withdrawing groups [11]. Thus, ArNH2 products can be obtained by (EWGs) in the α position and a suitable leaving reaction with 1-chloro-2,4,5-trimethylbenzene and 1- group [2]. In 1970, Bunnett applied this mechanism chloro-2,3,5-trimethylbenzene, o-MeOC6H4X (X = to unactivated aromatic halides [3]. Later on, other Br or I), 2-iodo-1,3-dimethylbenzene, PhOPh, 3- substrates such as vinyl halides, perfluoroalkyl bromothiophene, and ArOP(O)(OEt)2, under K metal halides, alkylmercury chlorides, as well as cycloalkyl, reduction in liquid ammonia [11]. NH2ˉ ions react bridgehead, and neopentyl halides were reported to under photoinitiation with 2-bromo-1,3,5- react by this mechanism. The process has a trimethylbenzene with good substitution yields (70%) considerably wide scope. Many substituents, such as [12]. alkyl groups, OR, OAr, SAr, CF3, CO2R, NH2, NHCOR, NHBoc, SO2R, CN, COAr, NR2, and F are PhNHˉ ions reacts in the presence of K metal with compatible with the reaction. In addition to halides, PhI, and substitution occurs not only at nitrogen but many other leaving groups are known for this also at ortho and para carbons of the phenyl ring. On reaction including (EtO)2P(O)Oˉ, RSˉ, ArOSˉ, the other hand, the 2-naphthylamide ion reacts under ArO2Sˉ, PhSeˉ, Ph2S, RSN2 (R = t-Bu, Ph), BF4N2, photoinitiation with PhI, p-MeOC6H4I, and 1- R3N, N2, N3ˉ, NO2ˉ, and HgXˉ. Thus, ArOH and iodonaphthalene in liquid ammonia to give 1-aryl-2- ArNH2 are ultimately the leaving groups through naphthylamines in good yields [13]. The SRN1 phosphate esters and ammonium salts. reaction is quite versatile in that other nucleophiles The SRN1 mechanism has proved to be an important for this reaction can be derived from P [14], As [15], route to ring-closure reactions, mainly in aromatic S [16], Se [17], and Te [18]. systems. The synthesis of indoles, carbazoles, isoquinolones, and other heterocycles, as well as a large number of natural products, has been achieved by this process. Several reviews have been published 3 2 on the SRN1 mechanism for substitution at sp and sp carbons [4]. Aromatic photo-initiated substitutions [5] as well as reactions performed under electrochemical catalysis [6, 7], convey the scope and the synthetic applications of this process [8]. In the initiation step of the SRN1 mechanism, the radical anion of substrate RX˙ˉ can be formed upon ET from the nucleophile or from a suitable electron source; the ET to unsubstituted alkyl halides is proposed to be a dissociative reaction [9]. RX˙ˉ fragments to afford the radical R˙ and the anion of the leaving group. The radical thus formed can react with the nucleophile to give the radical anion of the substitution product RNu˙ˉ, which by ET to the substrate forms the intermediates required to Scheme 4. The first example of an SRN1 type propagate the cycle. The termination steps depend on process with the mechanism below the substrate, the nucleophile, and the experimental conditions (Scheme 3) [10]. Reactions of carboanions to afford a new C-C bond constitutes one of the more representative examples of SRN1 reactions with aromatic substrates. Carbanions derived from hydrocarbons, such as 1,3- pentadienyl, 1-(4-anisyl)propenyl, fluorenyl, and indenyl anions, have been studied along this line [19]. The regiochemistry of the coupling favors the formation of the more stable radical anion intermediate. When aromatic substrates with two leaving groups such as 3 react with enolates, mono and disubstituted products can be obtained, depending on the nature and the position of the Scheme 3. Representation of the mechanism of the leaving group and on the nucleophile. Upon SRN1 reaction receiving an electron, substrate 3 forms the radical Nitrogen anion is a common nucleophile in the anion 3˙ˉ, which fragments at the more labile C-X SRN1 reaction. The first example of an SRN1 type bond to give radical 4. Then, this radical process was the reaction of ArX with the NH2ˉ ion intermediate 4 reacts with the nucleophile to form

International Journal of Advanced Scientific Research and Management, Volume 4 Issue 1, Jan 2019 www.ijasrm.com

ISSN 2455-6378

the radical anion 5. This radical anion can transfer allows efficient formation of diarly ketones upon the extra electron to another molecule of 124 reaction with acylchloride. (ETinter) to furnish product 6, or to the second C-Y bond by an intramolecular ET (ETintra). If ETintra There has been much study into the use of ring occurs, 5 fragments to afford radical 7, which by closing SRN1 reactions. These reactions work through coupling with the nucleophile followed by an ET the SRN1 substitution of aromatic compounds that reaction, generates the disubstitution product 8 have an appropriate substituent (Z) ortho to the (Scheme 5). This behavior is observed with dihalo leaving group, such as 10, which reacts with a substrates, not only with anions derived from ketones nucleophile to afford product 11. The ring-closure but with other nucleophiles as well [20]. product 12 is obtained by the reaction between the (Nu) and (Z) groups.

Scheme 5. Two possible pathways in SRN1 reactions with two leaving groups Scheme 7. Dual role of aromatic substituents as directing groups and reactive pendants for Transition metals such as Sn can help in generating cyclization. the nucleophile in the SRN1 reaction. For example, the leaving group ability of the Me Sn group in 3 For example the S 1 approach can be used as a nucleophilic substitutions allows the synthesis of RN route to isoquinoline rings and derivatives by asymmetric diaryl ketones in good yields (40-78%) reaction of o-iodobenzylamines with enolate ions through the reaction of Me SnAr with acyl chloride. 3 under irradiation. The substitution product 13 reacts These reactions are completely regioselective, further by ring closure to give product 14. If 14 is allowing the synthesis of diarylketones not usually treated with NaBH , tetrahydroisoquinolines 15 are available under Friedel-Crafts reactions. The reaction 4 obtained. On the other hand, treatment with Pd/C of stannane 9 with PhCOCl in PhCl as solvent, for provides isoquinoline derivatives 16 (Scheme 8) instance, furnished diarylketone 10 in 78% yield [23]. For more examples of the S 1 reaction see [21]. Specific di- and triketones are obtained in good RN “The S 1 Reaction” [24]. The atomic oxygen to excellent yields (45-83%, Scheme 6) [22]. RN radical anion plays a key role in a number of biological reactions [25]. The carbonate radical anion (CO3˙ˉ) is an important oxidant in cellular environments[26].

Scheme 6. The leaving group ability of Me3Sn

International Journal of Advanced Scientific Research and Management, Volume 4 Issue 1, Jan 2019 www.ijasrm.com

ISSN 2455-6378

have been studied as well. Ring opening reactions of this nature are still in infancy though, as kinetic data is virtually non-existent for aliphatic amine radical cations. Theoretical and experimental studies demonstrate that the cyclopropylamine radical cation undergoes barrier-less ring openings in both gas and solution (Freon) phase [34]. The distonic ring- opened radical-cation isomerizes via successive 1,2- hydride migration (Scheme 9) [35]. Ring-opened cyclopropylamine radical cations preferentially form the radical cation of allylamine 17.

Scheme 9. Ring openings of aliphatic cyclopropylamine radical cation and subsequent 1,2- hydride migration.

Rings opening through radical cation intermediates can also be used for ring expansion. Siloxy cyclopropane radical cations are key intermediates in Scheme 8. Synthesis of tetrahydroisoquinolines synthesis of larger ring systems wherein the radical (15) and isoquinolines (16) from o-iodobenzylamines cation ring opens. Without nucleophilic assistance to a distonic radical cation, subsequent loss of the silane and ˉCH2COR anions by SRN1-ring-closure sequence. group forms a β-keto radical [36]. These β-keto radicals can undergo further intramolecular addition Reactions that proceed through radical cations have to π systems. Transition state calculations by Mattay not garnered as much attention as the other radical and coworkers on (bicyclo[4.1.0]heptan-1- processes. Currently, only a small fraction of yloxy)trimethylsilane determined that endocyclic preparative reactions is based on electron transfer bond cleavage of the cyclopropane ring occurs processes [27]. Examples include the Birch predominantly [37]. Experimental work with reduction [28], acyloin condensation [29], Ullman analogous compounds is supported by Hasegawa coupling [30], formation of Grignard reagents [31], [38]. Further study of the regioselectivity of the the radical cation catalyzed Diels-Alder reaction cleavage of the bonds in these bicyclic compounds (Scheme 10) revealed that (i) photochemically [32], and the above mentioned SRN1 reaction [33]. As mentioned before, the major reason for the induced electron transfer and chemically induced scarcity of radical cation ET reactions in synthesis is oxidation (by tri-bromophenylaminyl radical cation) due to the difficulty in controlling the various caused ring opening to occur via different pathways, reaction events involving odd-electron species, as evidenced by observed products and (ii) the regardless of whether a catalytic (Figure 1a) or presence of a nucleophile in chemically oxidized stoichiometric transformation is considered (Figure systems enhances the ability of the radical cation to 1b). This section will briefly outline select examples undergo desilylation thus increasing reaction of radical cations in synthesis. efficiency. In addition to utility in synthesis, N- cyclopropyl substituted radical cations have been interesting target molecules for use as mechanistic probes and radical clocks.

N-alkyl-N-cyclopropylaniline radical cations have also been investigated in ring opening processes. N- alkyl-N-cyclopropylanilines have been employed previously as mechanistic probes in nitrosations of aromatic amines where ring opening is an indicator Figure 1. Reaction of odd-radical species in of radical cation intermediates. Nitrosation of N- catalytic (a) and stoichiometric amounts (b)

Similar to the cyclopropane ring opening reactions involving radical anions, radical cation ring openings

International Journal of Advanced Scientific Research and Management, Volume 4 Issue 1, Jan 2019 www.ijasrm.com

ISSN 2455-6378

Scheme 12. Photocatalytic oxygenation of anthracene by O2 with Acr+-Mes

A couple of decades ago it was observed that σ C- H˙+ deprotonations occurred through the arylation of alkanes upon PET with TCB 20 or CA (Scheme 13) [44, 45]. In 19˙+ deprotonation at the tertiary carbon atom is always favored. For more examples on the mechanistic insights of reactions involving radical cations see review by Schmittel and Burghart [46]. Scheme 10. Spirocyclic cyclopropane radical cation For more photochemical reactions involving radical exhibits regioselectivity during ring opening as cations see “Photoinduced Reactions of Radical Ions determined by mode of radical cation generation via Charge Separation”[47]. alkyl-N-cyclopropylanilines in acidic media (Scheme 11) proceeds through an aminyl radical cation intermediate. This intermediate undergoes regioselective ring opening and reacts further to form N-alkyl-N-nitroanilines [39].

Scheme 11. Nitrosation mechanism for N, N- dialkylanilines Scheme 13. σ C-H˙+ deprotonation in arylation of Photoirradiation is another common method of adamantine inducing radical transformations that go through radical cation intermediates. For example the The use of small organic molecules to catalyze photocatalytic oxygenation of anthracene by O2 with asymmetric transformations has been known since Acr+-Mes complex 18 (Scheme 12) to form the early 1970’s (e.g. the Hajos-Parrish-Eder-Sauer- anthraquinone [40]. The photo-catalytic oxygenation Wiechert Reaction). However, the recognition of this of anthracenes is initiated by photoexcitation of reaction’s mechanism as a general mode of carbonyl Acr+-Mes, which results in the formation of the activation was overlooked. In 2000, general modes electron-transfer state (Acr˙-Mes˙+), followed by of activation using small organic molecules electron transfer from anthracenes to the Mes˙+ (secondary amines) were introduced, namely moiety together with electron transfer from the Acr˙ enamine and iminium ion catalysis. Recently, moiety to O2 [41]. The resulting anthracene radical MacMillan and Sibi have developed catalysis based cation undergoes radical coupling reactions with O2˙ˉ on single-electron oxidation of transiently produced, to produce the epidioxyanthracene (An-O2). The electron rich enamines has introduced a new mode of mechanism of the photocatalytic conversion of An- activation termed SOMO organocatalysis. Activation O2 to 10-hydroxyanthrone is shown in Scheme 12. by this method allows for reaction with a variety of weakly nucleophilic substrates incompatible with Photochemistry is useful in reactions that proceed previous methods. For successful SOMO through radical cations. Evidence for σ C-H˙+ organocatalysis, an equilibrium population of cleavage was deduced from pulse radiolysis studies enamine must undergo preferential oxidation, the [42]. From ESR investigations, it was suggested that amine catalyst must enforce high levels of deprotonation preferentially occurs at the C-H bond enantiocontrol in the coupling of the radical cation with the highest unpaired electron density [43]. with nucleophiles, and the general reactivity mode must be useful in other enantioselective reaction.

International Journal of Advanced Scientific Research and Management, Volume 4 Issue 1, Jan 2019 www.ijasrm.com

ISSN 2455-6378

As of recent, enantioselective oganocatalysis to form carbon-carbon bonds has received much attention. The chemistry of radical reactions has a long history MacMillan and Sibi have developed in the realm of but continues to grow. The synthetic utility of radical organocatalysis, in which singly occupied molecular reactions is enhanced by their functional group orbital (SOMO) activation is used for tolerance as well as by the relatively mild conditions enantioselective α-allylation [48, 49], α-vinylation (no need for strong acids and bases) under which [50], α-oxygenation of aldehydes [51], and α- radicals can be generated and it is further expanded allylation of ketones [52]. The SOMO catalysis by the ability of radicals to carry on multiple proceeds by single-electron oxidation of a transiently sequential bond-forming reactions in intramolecular formed enamine to give the radical cation (SOMO of cascades. The combination of these features allowed activated species). For example, propanal 21 reacts for the synthesis of many complex natural products with imidazolidinone catalyst 22 to form eneamine with remarkable efficiencies. The future 23. This can then go through a one-electron development of this area benefits strongly from the oxidation, using a reagent such as ceric ammonium abundance of high quality kinetic data and modern nitrate (CAN), to form the radical cation 24 (Scheme computational techniques capable of accurate 14). description of potential energy profiles for radical transformations.

References

Scheme 14. Catalytic chemical steps leading to [1] Tanko J. M., and Drumright R. E., J. Am. Chem. formation of SOMO-activated intermediate Soc., 1990, 112, 5362–5363 (Year). [2] a) Kornblum N., Michel R. E., and Kerber Reaction of octanal and N-tert-butyl carbamoyl R. C., J. Am. Chem. Soc., 1966, 88, 5662– 5662. b) Russell G. A. and Danen W. C., J. pyrrole under the SOMO activation conditions enables formyl α-arylation with enantioselectivity Am. Chem. Soc., 1966, 88, 5663–5665. [3] Kim J. K., and Bunnett J. F., J. Am. Chem. and in excellent yields (Scheme 15a). It has also been found that unsaturated aldehydes rapidly Soc., 1970, 92, 7463–7464. [4] Pierini A. B., Peñéñory A. B. and Rossi R. undergo enantioselective cyclization with trapping of an exogenous halide. α-Allylation of ketones via a A, Chem. Rev., 2003, 103, 71–168. similar reaction design was developed later (Scheme [5] Bowman W. R., Chem. Soc. Rev., 1988, 17, 15b). 283–316. [6] Savéant J.-M., Acc. Chem. Res., 1993, 26, 455–461. [7] Andrieux C. P., Savéant J.-M. and Hapiot P., Chem. Rev., 1990, 90, 723–738. [8] Kornblum N., Aldrichim. Acta, 1990, 23, 71–78. [9] Savéant J.-M., Adv. Phys. Org. Chem., 2000, 35, 117–192. [10] Chopa A. B., Silbestri G. F., Lockhart M. T., and Masson R. B., J. Organomet. Chem., 2006, 691, 1520–1524. [11] Kim J. K., and Bunnett J. F., J. Am. Chem. Soc., 1970, 92, 7463–7464. [12] Bardón A., Alonso R. A.and Rossi R. A., J. Org. Chem., 1984, 49, 3584–3587. [13] Pierini A. B., Baumgartner M. T., and Rossi Scheme 15. α-Allylation of aldehydes (a) and R. A., Tetrahedron Lett., 1987, 28, 4653– ketone (b) through SOMO catalysis with high yields 4656. and ee [14] de Bueger B., Defacqz N., Touillaux R., et al ., Synthesis, 1999, 8, 1368–1372. [15] Rossi R. A., Alons R. A. o, and Palacios S. 3. Conclusions M., J. Org. Chem., 1981, 46, 2498–2502. [16] Ginsburg H., Eugelmans R. B., Tetrahedron Radical reactions have proven themselves to be Lett., 1987, 28, 413–414. among the most powerful and adaptable tools in the [17] Peñéñory A. B., and Rossi R. A., J. Org. synthetic chemists arsenal. Chem., 1981, 46, 4580–4582.

International Journal of Advanced Scientific Research and Management, Volume 4 Issue 1, Jan 2019 www.ijasrm.com

ISSN 2455-6378

[18] Pierini A. B., and Rossi R. A., J. Org. [36] 1 B. H. Lee, J. M. Sung, S. C. Blackstock, Chem., 1979, 44, 4667–4673. and J. K. Cha, J. Am. Chem. Soc., 2001, 123, [19] Bunnett J. F. and Singh P., J. Org. Chem., 11322–11324. 1981, 46, 5022–5025. [37] J. Mattay, P. A. Waske, and H. Rinderhagen, [20] Pierini A. B., Peñéñory A. B. and Rossi R. Tetrahedron, 2006, 62, 6589–6593. A., Chem.Rev., 2003, 103, 71–168. [38] E. Hasegawa, N. Yamaguchi, H. Muraoka, [21] Chopa A. B., Silbestri G. F., Lockhart M. T. and H. Tsuchida, Org. Lett., 2007, 9, 2811– and Masson R. B., J. Organomet. Chem., 2814. 2006, 691, 1520–1524. [39] a) R. N. Loeppky, T. Theiss, R. Hastings, et [22] Silbestri G. F., et al ., Badajoz M. A., Lo al ., J. Am. Chem. Soc., 1998, 120, 5193– Fiego M. J., J. Org. Chem., 2008, 73, 9184– 5202. b) R. N. Loeppky, and S. Elomari, J. 9187. Org. Chem., 2000, 65, 96–103. [23] Roussi G., Chastanet J.and. Beugelmans R., [40] H. Kotani, K. Ohkubo, and S. Fukuzumi, J. Tetrahedron, 1984, 40, 311–314. Am. Chem. Soc., 2004, 126, 15999–16006. [24] Bardagí J. I., Vaillard V. A., Rossi R. A., [41] S. Fukuzumi, H. Kotani, K. Ohkubo, et al ., The SRN1 Reaction. In Encyclopedia of J. Am. Chem. Soc., 2004, 126, 1600–1601. Radicals in Chemistry, Biology and [42] D. B. Clark, M. Fleischmann, and D. Materials; C. Chatgilialoglu, A. Studer, Pletcher, J. Chem. Soc. Perkin Trans. 2, Eds.; John Wiley and Sons: Chichester, 1973, 1578-1581. U.K., 2012. [43] a) K. Toriyama, K. Nunorne, and M. [25] J. Lee, and J. J. Grabowski, Chem. Rev., Iwasaki, J. Phys. Chem., 1986, 90, 6836- 1992, 92, 1611-1647. 6842. b) K. Toriyama, K. Nunome, and M. [26] V. Shafirovivh, A. Dourandin, W. Huang, Iwasaki, J. Chem. Phys., 1982, 77, 5891- and N. E. Geacintov, J. Biol. Chem., 2001, 5912. 276, 24621-24626. [44] M. Mella, M. Freccero, and A. Albini, [27] a) P. Haberfield, J. Am. Chem. Soc., 1995, Tetrahedron, 1996, 52, 5533-5548. 117, 3314-3315. b) B. Speiser, Angew. [45] M. Mella, M. Freccero, T. Soldi, E. Fasani, Chem. Int. Ed. Engl. 1996, 35, 2471-2471. and A. Albini, J. Org. Chem., 1996, 61, [28] P. W. Rabideau, and Z. Marcinow, Org. 1413-1422. React., 1992, 42, 1-334. [46] M. Schmittel, and A. Burghart, Angew. [29] J. J. Bloomfield, D. C. Owsley, and J. M. Chem. Int. Ed. Engl., 1997, 36, 2550-2589. Nelke, Org. React., 1976, 23, 259-403. [47] S. Fukuzumi, and K. Ohkubo, Photoinduced [30] M. Xi, and B. E. Bent, J. Am. Chem. Soc., Reactions of Radical Ions via Charge 1993, 115, 7426-7433. Separation. In Encyclopedia of Radicals in [31] J. F. Garst, Acc. Chem. Res., 1991, 24, 95- Chemistry, Biology and Materials; C. 97. Chatgilialoglu, A. Studer, Eds.; John Wiley [32] a) N. L. Bauld, Tetrahedron, 1989, 45, and Sons: Chichester, U.K., 2012. 5307-5363. b) N. L. Bauld, and R. Pabon, J. [48] T. D. Beeson, A. Mastracchio, J. –B. Hong, Am. Chem. Soc., 1983, 105, 633-634. K. Ashton, and D. W. C. MacMillan, [33] a) G. A. Russell, Adv. Phys. Org. Chem., Science, 2007, 316, 582-585. 1987, 23, 271-322. b) J. F. Bunnett, Acc. [49] H. Y. Jang, J. B. Hong, and D. W. Chem. Res., 1978, 11, 413-420. MacMillan, J. Am. Chem. Soc., 2007, 129, [34] a) M.-T. Nguyen, S. Creve, and T.-K. Ha, 7004-7005. Chem. Phys. Lett., 1998, 293, 90–96. b) W. [50] H. Kim, and D. W. MacMillan, J. Am. F. Richardson, H. F. King, and A. L. Chem. Soc., 2008, 130, 398-399. Cooksy, J. Org. Chem., 2003, 68, 9441– [51] M. P. Sibi, and M. Hasegawa, J. Am. Chem. 9452. Soc., 2007, 129, 4124-4125. [35] X. Z. Qin, and F. Williams, J. Am. Chem. [52] A. Mastracchio, A. A. Warkentin, A. M. Soc., 1987, 109, 595–597. Walji, and D. W. C. MacMillan, Proc. Natl. Acad. Sci. USA, 2010, 107, 20648-20651.